Glucagon-like Peptide-1 Agonists Research Articles

Dietary Modulations in Preventing Cardiometabolic Risk in Individuals with Type 2 Diabetes.

Type 2 diabetes mellitus (T2DM) is a complex health issue include obesity, high cholesterol, high blood pressure, and chronic inflammation that increase the risk of cardiovascular diseases (CVDs). CVDs are of great concern in the disease progression and prognosis of T2DM. This review is a comprehensive examination of the literature on the relationship between T2DM and cardiovascular risk, nutrition-related cardiometabolic risk (CMR) factors, and impact of dietary modulations on CMR. In recent years the researches has been focus on the importance of a comprehensive treatment approach like dietary modulations to address multiple cardiovascular risk reductions, including hypertension and dyslipidemia. Modulation of dietary patterns are the most promising interventions to prevent CMR factors and T2DM via affecting the body weight, glucose control, and microbial diversity of individuals. Current evidence suggests that high-quality dietary patterns such as the Dietary Approaches to Stop Hypertension (DASH) eating plan and the Mediterranean diet is important in the metabolic control processes of T2DM with anti-inflammatory and antioxidant compounds, glucagon-like peptide agonist compounds, and intestinal microbiota changes. Nutrition plays a critical role in preventing and improving CVD outcomes in patients with T2DM. Dietary modulations should be planned considering individual differences in responses to dietary composition and nutritional changes, personal preferences, eating behaviors and gut microbiota differences.

ADVERSE EVENTS ASSOCIATED WITH GLP1–RECEPTOR AGONISTS TREATMENT IN DIABETIC PATIENTS WITH HIGH CARDIOVASCULAR RISK: A META–ANALYSIS

Abstract Background GLP1–receptor agonists (GLP1–RA) have been associated with a reduction of cardiovascular (CV) outcomes in diabetic patients with high cardiovascular risk. However, these drugs have some adverse effects. The aim of this study was to assess the relative risk (RR) of adverse effects in patients with a high risk of developing CV disease treated with GLP1–agonists. Methods we considered randomized controlled trials (RCTs) aimed to assess the cardiovascular effects of GLP1–RA in diabetic patients with high CV risk. The following outcomes were explored: pancreatitis, severe hypoglycemia, renal and urinary serious adverse events (SAE), gastrointestinal SAE and AE, pancreatic cancer, and neoplasms. Results 8 RCTs, enrolling 60008 patients, were included in the analysis. There was no difference between GLP1–RA and placebo in the risk of pancreatitis (RR 0.99; 95% CI 0.73–1.35; p=0.972), severe hypoglycemia (0.93; 95% CI 0.76–1.15; p=0.501), renal and urinary SAE (0.94; 95% CI 0.82–1.07; p=0.339), pancreatic cancer (RR 0.98; 95% CI 0.56–1.70; p=0.936) and neoplasms (RR 1.02; 95% CI 0.95–1.09; p=0.547) (Fig 1 A e B). Conversely, GLP1–agonist treatment was associated with an increased risk of gastrointestinal AE (RR 1.95; 95% CI 1.23–3.06; p=0.004) (Fig 2). However, when gastrointestinal SAE were considered, GLP1–agonists demonstrated similar risk compared to placebo (RR 1.09; 95% CI 0.92–1.28; p= 0.318) (Fig 2). Conclusion in diabetic patients with high cardiovascular risk, the treatment with GLP1–RA has been associated with an increased risk of gastrointestinal AE. No difference in severe gastrointestinal AE has been associated with GLP1–RA.

Cardioprotective effects of glucagon-like peptide 1 receptor agonists in heart failure: Myth or truth?

Therapy with glucagon-like peptide 1 (GLP1) receptor agonists has raised great interest for its beneficial cardiovascular effects in preventing atherosclerosis and heart failure-related outcomes. However, while evidence about atherosclerosis consistently suggests a cardioprotective potential with class effect, controversies remain on its impact on heart failure. GLP1 receptor agonists appear to prevent hospitalization for new-onset heart failure and reduce symptoms in heart failure with preserved ejection fraction (as demonstrated by the recent STEP-HFpEF Trial). Still, GLP1 agonism has resulted in neutral or even harmful effects in patients with established heart failure with reduced ejection fraction (the LIVE trial). GLP1 receptor agonists benefit the cardiovascular system indirectly through their marked metabolic effects (improved weight management, glycemic control, blood pressure, systemic and tissue inflammation), while direct effects on the heart have been questioned. Nonetheless, weight loss alone achieved through GLP1 receptor agonists has failed in improving left ventricular functions. Tirzepatide is a dual agonist of GLP1 and glucose-dependent insulinotropic polypeptide, representing an innovative treatment option in diabetes with a major impact on weight loss and promising cardiovascular benefits. Whether this class of therapies is going to change the history of heart failure is an ongoing debate.

GLP-1 agonists and hair loss: a call for further investigation.

The widespread adoption of glucagon-like peptide-1 (GLP-1) agonists in treating type 2 diabetes mellitus (T2DM) and obesity has sparked investigations into their impact on hair health, an area characterized by diverse conjectures. Some propose potential risks such as disrupted hair growth cycles or premature androgenetic alopecia (AGA), while others suggest benefits linked to improved insulin sensitivity and enhanced scalp blood circulation. However, despite these theoretical underpinnings, clinical evidence linking GLP-1 agonists to hair loss remains sparse. The necessity for vigilant patient monitoring and collaborative efforts cannot be overstressed in comprehensively addressing any potential consequences of GLP-1 agonist therapy on hair health as their use continues to expand.

Reduced Incretin Receptor Trafficking upon Activation Enhances Glycemic Control and Reverses Obesity in Diet-Induced Obese Mice.

Activation of incretin receptors by their cognate agonists augments sustained cAMP generation both from the plasma membrane as well as from the endosome. To address the functional outcome of this spatiotemporal signaling, we developed a non-acylated glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor dual agonist I-M-150847 that reduced receptor internalization following activation of the incretin receptors. The incretin receptor dual agonist I-M-150847 was developed by replacing the tryptophan cage of exendin-4 tyrosine substituted at the amino terminus with the C-terminal undecapeptide sequence of oxyntomodulin that placed lysine 30 of I-M-150847 in frame with the corresponding lysine residue of GIP. The peptide I-M-150847 is a partial agonist of GLP-1R and GIPR; however, the receptors, upon activation by I-M-150847, undergo reduced internalization that promotes agonist-mediated iterative cAMP signaling and augments glucose-stimulated insulin exocytosis in pancreatic beta cells. Chronic administration of I-M-150847 improved glycemic control, enhanced insulin sensitivity, and provided profound weight loss in diet-induced obese (DIO) mice. Our results demonstrated that despite being a partial agonist, I-M-150847, by reducing the receptor internalization upon activation, enhanced the incretin effect and reversed obesity.

Safety and efficacy of GLP-1 and glucagon receptor dual agonist for the treatment of type 2 diabetes and obesity: a systematic review and meta-analysis of randomized controlled trials.

This study aimed to investigate the effects of randomized, placebo-controlled trials involving the GLP-1 and glucagon receptor dual agonists, mazdutide, and cotadutide, on glycaemic control and body weight changes in individuals with type 2 diabetes mellitus (T2DM), obesity, or both. We conducted searches in Medline, PubMed, Scopus, the Cochrane database, and Web of Science up to March 5, 2024. The primary outcomes assessed were changes in HbA1c level and percentage changes in body weight from baseline (CFB). Eleven studies and four unpublished trials were included. The pooled meta-analysis revealed a significant reduction in HbA1c (MD = -0.63%; 95% CI = [-0.82, -0.44]; P < 0.00001), fasting plasma glucose (MD = -1.71 mmol/L; 95% CI = [-2.31, -1.10]; P < 0.00001), and percentage change in body weight (MD = -4.16%; 95% CI = [-5.41, -2.92]; P < 0.00001). Safety analysis revealed no significant change in serious adverse events (OR = 1.03; 95% CI = [0.61, 1.75]; P = 0.91), but there were significantly higher odds of treatment-emergent adverse events (OR = 2.52; 95% CI = [1.92, 3.30]; P < 0.00001) and vomiting (OR = 6.05; 95% CI = [3.52, 10.40]; P < 0.00001). These results suggest that mazdutide and cotadutide are effective for glycaemic control and weight reduction in individuals with T2DM, obesity, or both.

Medical treatment of pediatric obesity

Background: The increasing prevalence of pediatric obesity over the past few decades has become a serious public health concern. Quarantine measures during the coronavirus disease pandemic have led to an increase in childhood obesity rates. Children with obesity are at greater risk for type 2 diabetes, hypertension, dyslipidemia, polycystic ovary syndrome, obstructive sleep apnea, and adult obesity. Lifestyle modification therapy is the firstline treatment for pediatric obesity. Pharmacotherapy is the next logical treatment option in patients in whom lifestyle modifications alone are ineffective.Current Concepts: Anti-obesity medications for pediatric obesity include metformin, orlistat, glucagon-like peptide-1 agonists, phentermine, and phentermine/topiramate combination. Metformin, a medication used for type 2 diabetes has not been approved for treatment of pediatric obesity. Orlistat, a lipase inhibitor, prevents fat absorption from the human diet. Liraglutide, a glucagon-like peptide-1 agonist, is associated with decreased gastric emptying, increased satiety, and appetite suppression. Phentermine, a norepinephrine reuptake inhibitor, is approved by the Food and Drug Administration for short-term treatment of patients aged &gt;16 years. Phentermine/topiramate is a combination of the conventional anti-obesity medication, phentermine and an antiepileptic agent, topiramate that is commonly associated with weight loss as an adverse effect.Discussion and Conclusion: Anti-obesity treatment may serve as the next logical therapeutic option for pediatric obesity. However, sufficient lifestyle modification therapy should be attempted before considering medication, and anti-obesity medications should preferably be used in combination with lifestyle modifications. Monitoring growth and pubertal development during anti-obesity treatment is essential to ensure healthy development of children and adolescents.

Abstract PO5-12-03: Cardiovascular Toxicities in Breast Cancer Survivors

Abstract Background: Chemotherapy, despite its effectiveness, presents drawbacks in breast cancer patients due to its side effects. Fatigue, hair loss, nausea, and anemia are among the many symptoms associated with chemotherapy. Moreover, chemotherapy can lead to cardiovascular diseases, including cardiac arrhythmias, hypertension, heart failure, heart attacks, and cardiomyopathy, particularly with the use of anthracyclines and HER-2-targeted agents. Risk factors such as weight, age, race, comorbidities (e.g., obesity, diabetes, hyperlipidemia), and radiation exposure further increase these risks. Despite these potential complications, guidelines are just emerging aiming to prevent these cardiovascular complications in breast cancer patients. Untreated cardiovascular abnormalities can have long-term effects on breast cancer survivors. Our aim is to analyze the relationships between breast cancer treatment and cardiovascular abnormalities, examining associations with various factors, including race, BMI, and age in a majority Hispanic cohort of breast cancer survivors. Methods: retrospective, single institution study data from a total of 53 patients treated with chemotherapy with either anthracyclines and/or HER 2 directed therapy with curative intent between 2018-2020. Our analysis included basic demographic information, menopausal status, breast cancer type, treatment types, use of cardio-protective medications, and cardiovascular effects (both pre-existing and developed during treatment). Results: Our sample of 50 women primarily comprised Hispanic individuals (73%), most of whom were postmenopausal (86%), with an average age of 63 years (range 35-86). Among the breast cancer types identified, 35 were hormone-positive, 8 were HER-2 positive, and 10 were triple negative. 72% of the patients received adjuvant hormonal therapy. 18% of the population received anthracycline-based treatment, 8% received Her 2 directed therapy and 2 % received Immune check point inhibitors. Radiation therapy was administered to 50% of the patients. The most prevalent cardiovascular disease observed was hypertension, affecting 62% of patients, followed by type 2 diabetes (38%), hyperlipidemia (34%), stroke (8%), and heart attack (6%). The predominant cardioprotective medications used were ACE inhibitors/ARBs (48%), followed by statins (46%), beta-blockers (20%), aspirin (16%), and GLP-1 agonists (14%). Conclusion: Our analysis revealed a high prevalence of cardiovascular conditions among breast cancer survivors treated with chemotherapy in a majority Hispanic cohort of patients. This population has been linked to higher risk of developing comorbidities such as diabetes, obesity and hypertension. Further analysis evaluating risk factors and implementation of treatment strategies to minimize adverse effects is needed in this population. Citation Format: Victoria Ayodele, Emily Sherry, Marcela Mazo-Canola. Cardiovascular Toxicities in Breast Cancer Survivors [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-12-03.

Exploring the Impact of Sodium-Glucose Cotransporter-2 Inhibitors on Genitourinary Toxicities in Prostate Cancer Patients Undergoing Radiation Therapy: A Case Study and Discussion

Radiation therapy is a common treatment modality offered to patients with localized prostate cancer. It can be associated with early radiation-induced toxicities including dysuria, nocturia, frequency, urgency, spasm, and, rarely, hematuria. Early toxicities usually resolve once the treatment period has ended. Chronic toxicities are less common, and rarely, patients may experience radiation-induced hemorrhagic cystitis and hematuria months or years after radiation. We herein describe the case of a 65-year-old man with a past medical history of type-2 diabetes mellitus who experienced hemorrhagic cystitis for months following his radiation therapy. The patient was on sodium-glucose cotransporter-2 inhibitor therapy (empagliflozin), which we highlight as a potential risk factor for hemorrhagic cystitis. After cessation of Jardiance and initiation of semaglutide (GLP-1 agonist), his urinary symptoms significantly improved. To the best of our knowledge, this is the first such case reported.

Moving from insulin substitution to the treatment of the underlying autoimmune disease in type 1 diabetes.

Currently a paradigm change occurs in type 1 diabetes from insulin substitution to the treatment of the underlying autoimmune disease. Teplizumab, a humanized monoclonal anti CD3 antibody, is the first FDA approved disease modifying treatment of preclinical stage 2 diabetes. Research of drugs like Golimumab, a monoclonal antibody specific for TNF alpha, baricitinib, a tyrosine kinase inhibitor, or frexalimab, a monoclonal antibody against the CD40-Ligand, is still ongoing. Repurposing drugs that have been used in other indications like the calcium channel blocker Verapamil, antithymocyte globulin (ATG), an antibody preparation used in solid organ transplantation, glucagon-like peptide-1 agonists, utilized in type 2 diabetes and obesity, or the antiviral drugs pleconaril and ribavirin have shown positive effects in preserving beta-cell function. While new therapies to halt autoimmunity and restore beta-cells in stages one to three are being developed, replacing beta-cell function via inducible pluripotent stem cells have shown glucose control and insulin independence in long-standing type 1 diabetes albeit with concomitant immunosuppression. Multicenter multinational initiatives developing a clinical trial network like INNODIA or a research platform with the goal of stopping type 1 diabetes in its early stages like EDENT1FI will be instrumental to study these new strategies.

Incretin-Based Weight Loss Pharmacotherapy: Can Resistance Exercise Optimize Changes in Body Composition?

This narrative review highlights the degree to which new antiobesity medications based on gut-derived nutrient-stimulated hormones (incretins) cause loss of lean mass, and the importance of resistance exercise to preserve muscle. Glucagon-like peptide 1 receptor agonists (GLP-1RA) induce substantial weight loss in randomized trials, effects that may be enhanced in combination with glucose-dependent insulinotropic polypeptide (GIP) receptor agonists. Liraglutide and semaglutide (GLP-1RA), tirzepatide (GLP-1 and GIP receptor dual agonist), and retatrutide (GLP-1, GIP, and glucagon receptor triple agonist) are peptides with incretin agonist activity that induce ∼15-24% weight loss in adults with overweight and obesity, alongside beneficial impacts on blood pressure, cholesterol, blood glucose, and insulin. However, these agents also cause rapid and significant loss of lean mass (∼10% or ∼6 kg), comparable to a decade or more of aging. Maintaining muscle mass and function as humans age is crucial to avoiding sarcopenia and frailty, which are strongly linked to morbidity and mortality. Studies indicate that supervised resistance exercise training interventions with a duration >10 weeks can elicit large increases in lean mass (∼3 kg) and strength (∼25%) in men and women. After a low-calorie diet, combining aerobic exercise with liraglutide improved weight loss maintenance compared with either alone. Retaining lean mass during incretin therapy could blunt body weight (and fat) regain on cessation of weight loss pharmacotherapy. We propose that tailored resistance exercise training be recommended as an adjunct to incretin therapy to optimize changes in body composition by preserving lean mass while achieving fat loss.

The efficacy and safety of GLP-1 receptor agonists in youth with type 2 diabetes: a meta-analysis

BackgroundGlucagon-like peptide 1 receptor agonists have been proven to be effective in adults with diabetes and children with obesity. However, children with type 2 diabetes constitute an underrepresented subpopulation with limited treatment options. This meta-analysis aimed to determine more precise estimates of the efficacy and safety of glucagon-like peptide-1 agonists in pediatric type 2 diabetes mellitus.MethodsThree databases were searched (PubMed, Embase, and Cochrane Central Register of Controlled Trials) for trials published until the end of March 2024. The search indexing terms included 3 categories: [1] type 2 diabetes mellitus [2], youth, and [3] glucagon-like peptide-1 receptor agonist (GLP-1 RA). Randomized controlled trials in youth with type 2 diabetes (age ≤ 18 years) that assessed anthropometric and metabolic parameters were included. A total of 1119 nonduplicate studies were retrieved, and 137 full-text articles were screened. The data were analyzed using mean differences (MDs) with 95% CIs and odds ratios (ORs) with 95% CIs. For outcomes with low heterogeneity, a fixed-effects model was used. Otherwise, we applied a random effects model. Our outcomes were Hb1Ac, fasting blood glucose (FBG), blood pressure, weight, and side effects.ResultsFive studies comprehending 415 children and adolescents were included. On average, GLP-1 RA reduced HbA1c levels (-1.01%; 95% CI, -1.26 to -0.76), fasting blood glucose levels (-1.88 mmol/L; 95% CI, -2.51 to -1.26), and body weight (-1.6 kg; 95% CI, -2.83 to -0.36). No significant reductions in systolic blood pressure (MD -0.19 mmHg; 95% CI, -3.9 to 3.52 mmHg) or diastolic blood pressure (MD 0.3 mmHg; 95% CI, -2.33 to 2.93 mmHg) were observed. Despite a higher incidence of side effects, withdrawal rates from the studies remained low.ConclusionsWithin this specific population, GLP-1 RAs exhibit a notable association with substantial reductions in HbA1c, FBG, and body weight. The administration of these medications is concurrent with an elevated incidence of side effects, which are predominantly gastrointestinal and tolerable.Trial registrationPROSPERO identifier: CRD42023393020.

Effectiveness of a hybrid approach in integrating GLP-1 agonists and lifestyle guidance for obesity and pre-diabetes management: RWE retrospective study

AimEmerging anti-obesity pharmacotherapy provides an option to correct maladaptive physiological and hormonal changes associated with obesity. One of the widely used medications in this context is glucagon-like peptide 1 (GLP-1) agonists. However, the misuse of these medications without any guidance and monitoring of lifestyle modifications can lead to unfavorable outcomes. The study aims to evaluate the effectiveness of a hybrid care model, incorporating GLP-1 and GLP-1/GIP agonist therapies, in managing obese patients with/without pre-diabetes. This study showcases the midway results of a 6-month program, which includes a multidisciplinary care team and digital technology for continuous engagement and monitoring of patients, both in-clinic and remotely. MethodsIn a retrospective observational study, 115 participants were treated with GLP-1s (semaglutide, tirzepatide, and liraglutide). Physicians, dietitians, and coaches worked together to support behavioral changes using a dedicated app provided to patients. At the care team end, an integrated portal enabled continuous data flow allowing for the care team to provide personalized care via chat at regular intervals. Data collected included food logs, continuous glucose monitoring (CGM), and digital biomarkers such as sleep and activity. ResultsAt the midpoint of the program, participants exhibited statistically significant improvements in various metabolic parameters. Mean weight reduction was 8 %, with significant reductions in BMI, fat mass, and cholesterol levels. 24 (20.9 %) of patients lost ≥5 % of body weight, 55 (47.8 %) patients lost ≥10 % weight, and 36 (31.3 %) patients lost ≥15 % weight. Sub-analysis of pre-diabetic patients (n=36) demonstrated substantial improvements, including control of pre-diabetes in 80.6 % of cases and reduced HbA1c levels back to normoglycemia (5.39 ± 0.27). ConclusionThe Zone.Health's program, which combines pharmacotherapy with continuous engagement and monitoring to enable sustainable lifestyle modifications, demonstrated significant improvements in weight, body composition, and metabolic markers. Pre-diabetes was also effectively addressed. It is necessary to conduct further research to assess the long-term sustainability and optimal adoption of such care models into clinical practice.

Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Systematic Review and Network Meta-analysis for the American College of Physicians.

Newer diabetes medications may have beneficial effects on mortality, cardiovascular outcomes, and renal outcomes. To evaluate the effectiveness, comparative effectiveness, and harms of sodium-glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP1) agonists, dipeptidyl peptidase-4 (DPP4) inhibitors, and long-acting insulins as monotherapy or combination therapy in adults with type 2 diabetes mellitus (T2DM). MEDLINE and EMBASE for randomized controlled trials (RCTs) published from 2010 through January 2023. RCTs lasting at least 52 weeks that included at least 500 adults with T2DM receiving eligible medications and reported any outcomes of interest. Data were abstracted by 1 reviewer and verified by a second. Independent, dual assessments of risk of bias and certainty of evidence (CoE) were done. A total of 130 publications from 84 RCTs were identified. CoE was appraised using GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria for direct, indirect, and network meta-analysis (NMA); the highest CoE was reported. Compared with usual care, SGLT2 inhibitors and GLP1 agonists reduce all-cause mortality (high CoE) and major adverse cardiovascular events (MACE) (moderate to high CoE), SGLT2 inhibitors reduce progression of chronic kidney disease (CKD) and heart failure hospitalizations and GLP1 agonists reduce stroke (high CoE), and SGLT2 inhibitors reduce serious adverse events and severe hypoglycemia (high CoE). The threshold for minimally important differences, which was predefined with the American College of Physicians Clinical Guidelines Committee, was not met for these outcomes. Compared with usual care, insulin, tirzepatide, and DPP4 inhibitors do not reduce all-cause mortality (low to high CoE). Compared with insulin, SGLT2 inhibitors and GLP1 agonists reduce all-cause mortality (low to moderate CoE). Compared with DPP4 inhibitors, GLP1 agonists reduce all-cause mortality (moderate CoE). Compared with DPP4 inhibitors and sulfonylurea (SU), SGLT2 inhibitors reduce MACE (moderate to high CoE). Compared with SU and insulin, SGLT2 inhibitors and GLP1 agonists reduce severe hypoglycemia (low to high CoE). Infrequent direct comparisons between drugs of interest; sparse data for NMA on most outcomes; possible incoherence due to differences in baseline patient characteristics and usual care; insufficient data on predefined subgroups, including demographic subgroups, patients with prior cardiovascular disease, and treatment-naive persons. In adults with T2DM, SGLT2 inhibitors and GLP1 agonists (but not DPP4 inhibitors, insulin, or tirzepatide) reduce all-cause mortality and MACE compared with usual care. SGLT2 inhibitors reduce CKD progression and heart failure hospitalization and GLP1 agonists reduce stroke compared with usual care. Serious adverse events and severe hypoglycemia are less frequent with SGLT2 inhibitors and GLP1 agonists than with insulin or SU. American College of Physicians. (PROSPERO: CRD42022322129).

Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Clinical Guideline From the American College of Physicians.

The American College of Physicians (ACP) developed this clinical guideline to update recommendations on newer pharmacologic treatments of type 2 diabetes. This clinical guideline is based on the best available evidence for effectiveness, comparative benefits and harms, consideration of patients' values and preferences, and costs. This clinical guideline is based on a systematic review of the effectiveness and harms of newer pharmacologic treatments of type 2 diabetes, including glucagon-like peptide-1 (GLP-1) agonists, a GLP-1 agonist and glucose-dependent insulinotropic polypeptide agonist, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, and long-acting insulins, used either as monotherapy or in combination with other medications. The Clinical Guidelines Committee prioritized the following outcomes, which were evaluated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach: all-cause mortality, major adverse cardiovascular events, myocardial infarction, stroke, hospitalization for congestive heart failure, progression of chronic kidney disease, serious adverse events, and severe hypoglycemia. Weight loss, as measured by percentage of participants who achieved at least 10% total body weight loss, was a prioritized outcome, but data were insufficient for network meta-analysis and were not rated with GRADE. The audience for this clinical guideline is physicians and other clinicians. The population is nonpregnant adults with type 2 diabetes. ACP recommends adding a sodium-glucose cotransporter-2 (SGLT-2) inhibitor or glucagon-like peptide-1 (GLP-1) agonist to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control (strong recommendation; high-certainty evidence). ACP recommends against adding a dipeptidyl peptidase-4 (DPP-4) inhibitor to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control to reduce morbidity and all-cause mortality (strong recommendation; high-certainty evidence).

Cost-Effectiveness of Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Systematic Review of Cost-Effectiveness Studies for the American College of Physicians.

In the United States, costs of antidiabetes medications exceed $327 billion. To systematically review cost-effectiveness analyses (CEAs) of newer antidiabetes medications for type 2 diabetes. Bibliographic databases from 1 January 2010 through 13 July 2023, limited to English. Nonindustry-funded CEAs, done from a U.S. perspective that estimated cost per quality-adjusted life-year (QALY) gained for newer antidiabetic medications. Two reviewers screened the literature; disagreements were resolved with a third reviewer. Cost-effectiveness analyses were reviewed for treatment comparisons, model inputs, and outcomes. Risk of bias (RoB) of the CEAs was assessed using Drummond criteria and certainty of evidence (CoE) was assessed using GRADE (Grading of Recommendations Assessment, Development, and Evaluations). Certainty of evidence was determined using cost per QALY thresholds predetermined by the American College of Physicians Clinical Guidelines Committee; low (>$150 000), intermediate ($50 to $150 000), or high (<$50 000) value per QALY compared with the alternative. Nine CEAs were eligible (2 low, 1 high, and 6 some concerns RoB), evaluating glucagon-like peptide-1 agonists (GLP1a), dipeptidyl peptidase-4 inhibitors (DPP4i), sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucose-dependent insulinotropic peptide agonist (GIP/GLP1a), and insulin. Comparators were metformin, sulfonylureas, neutral protamine Hagedorn (NPH) insulin, and others. Compared with metformin, GLP1a and SGLT2i are low value as first-line therapy (high CoE) but may be of intermediate value when added to metformin or background therapy compared with adding nothing (low CoE). Insulin analogues may be similarly effective but more expensive than NPH insulin (low CoE). The GIP/GLP1a value is uncertain (insufficient CoE). Cost-effectiveness analyses varied in methodological approach, assumptions, and drug comparisons. Risk of bias and GRADE method for CEAs are not well established. Glucagon-like peptide-1 agonists and SGLT2i are of low value as first-line therapy but may be of intermediate value when added to metformin or other background therapy compared with adding nothing. Other drugs and comparisons are of low or uncertain value. Results are sensitive to drug effectiveness and cost assumptions. American College of Physicians. (PROSPERO: CRD42022382315).

Glucagon-Like Peptide-1 Agonists and General Anesthesia: Perioperative Considerations and the Utility of Gastric Ultrasound.

Glucagon-like peptide-1 (GLP-1) agonists are very popular and useful medications for the treatment of type 2 diabetes mellitus and obesity. Potent gastric emptying delay is common with these medications, serving as a major contributor to the postprandial glycemic control and weight loss benefits of these medications. Recently, multiple case reports and studies indicating safety risks for these medications and their use in patients planning to undergo general anesthesia have been published, as retained gastric contents can lead to intraoperative aspiration. New guidelines for these medications have been released to guide clinical practice for anesthesiologists. Some degree of preoperative cessation of these medications is required. At this time, the ideal window for cessation of these medications to optimize clinical efficacy while reducing aspiration risks has not yet been well elaborated on. Aspiration of gastric contents can still occur despite appropriate preoperative fasting in patients taking GLP-1 agonists. Gastric ultrasound appears to be an effective and objective way of preoperatively assessing a patient's stomach contents to make decisions regarding anesthetic management for patients prescribed these medications. This practice is limited by a general lack of training and implementation in current anesthesiology practice.

A meta-analysis of the incidence of acne vulgaris in patients treated with GLP-1 agonists.

With the emerging popularity of GLP-1 receptor agonists, patients are noticing acne vulgaris side effects that are seemingly related to the concurrent treatment with the drug. Due to the correspondence between these drugs' relatively recent emergence in the U.S. market and their high demand, it is important to investigate what is currently known in the literature so that patients can be properly informed. The aim of this study is to investigate the relationship, or lack thereof, between glucagon like peptide 1 (GLP-1) receptor agonist usage and acne-related side effects in patients. A web-based analysis of 6 GLP-1 receptor agonists (3 with a once-weekly dosing schedule, and 3 with a once-daily dosing schedule) was conducted on PubMed online database. Boolean criteria were used to narrow the search. Included in the meta-analysis were 45 research articles that fulfilled the search criteria. The results of the search showed that from the following long-acting GLP-1 receptor agonists, dulaglutide, exenatide extended release, and semaglutide (Wegovy), no conclusive acne side effects were reported. In addition, the results also showed that from the following short-acting GLP-1 receptor agonists, liraglutide, lixisenatide, and semaglutide (Rybelsus), no conclusive acne side effects were reported. Limitations of this study include a limited amount of literature regarding the relationship between GLP-1 agonists and acne vulgaris. It is unlikely that GLP-1 agonists themselves are directly responsible for the acne that some patients may develop during treatment. Rather, it is more probable that the weight loss yielded by treatment with these drugs may induce intrinsic physiologic and hormonal changes that induce or exacerbate acne vulgaris in such patients.

Glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide agonists for the treatment of obesity and diabetes mellitus

Pharmaceutical interventions play a vital role in managing various conditions, including weight-related issues such as obesity. In this context, lifestyle changes are often challenging to maintain, especially for individuals struggling with this condition. Obesity is strongly linked to serious health conditions like cardiovascular disease and insulin resistance, leading to a cascade of health risks. Importantly, the development of effective and safe weight loss medications has been challenging. Diabetes mellitus (DM), the incidence of which is also rising, is closely related to obesity. The annual rate of DM cases has increased significantly, mirroring trends in obesity. Pharmaceutical companies have made significant progress in developing drugs that address both diabetes and obesity. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as a promising class of medications with dual benefits in managing diabetes and aiding weight loss such as semaglutide, liraglutide, dulaglutide, exenatide, among others. However, despite their effectiveness, they can be expensive. The availability of various GLP-1RAs offers flexibility in diabetes management, but the surge in their prescription has led to a global shortage. Health authorities are working to address this issue, while pharmaceutical companies are exploring new paths to improve the quality of these drugs. In this context, tirzepatide stands out as a medication targeting key hormones involved in obesity and DM. Another potential breakthrough, retatrutide, is also being developed for these two conditions, but it requires further research. In this paper, the authors address all the GLP-1RA options developed to date, covering their mechanisms of action, efficacy, and chemical structures, among other aspects.

Medical Weight Management Considerations in Plastic Surgery.

Obesity is one of the largest public health concerns in the US and has reached an epidemic scope over the last few decades. Plastic surgery in patients with obesity has been linked to higher complications both before and after weight loss. This article aims to discuss the evolution and current landscape of anti-obesity medications (AOMs) as they apply to the plastic surgeon. Although bariatric surgery has been effective in long-term treatment, new pharmacologic advances in GLP-1 agonists such as semaglutide have demonstrated promising effectiveness. These medications pose several unique challenges, particularly with regards to perioperative management and risk of weight regain after discontinuation. An understanding of these new pharmacologic agents is crucial for plastic surgeons as we treat those affected by obesity.