Review article: Pharmacologic management of obesity - updates on approved medications, indications and risks.

BACKGROUND: Obesity has reached epidemic proportions, with >40% of the US population affected. Although traditionally managed by lifestyle modification, and less frequently by bariatric therapies, there are significant pharmacological advancements. AIMS: To conduct a narrative review of the neurohormonal and physiological understanding of weight gain and obesity, and the development, clinical testing, indications, expected clinical outcomes, and associated risks of current FDA-approved and upcoming anti-obesity medications (AOMs). METHODS: We conducted a comprehensive review in PubMed for articles on pathophysiology and complications of obesity, including terms 'neurohormonal', 'obesity', 'incretin', and 'weight loss'. Next, we searched for clinical trial data of all FDA-approved AOMs, including both the generic and trade names of orlistat, phentermine/topiramate, bupropion/naltrexone, liraglutide, and semaglutide. Additional searches were conducted for tirzepatide and retatrutide - medications expecting regulatory approval. Searches included combinations of terms related to mechanism of action, indications, side effects, risks, and future directions. RESULTS: We reviewed the pathophysiology of obesity, including specific role of incretins and glucagon. Clinical data supporting the use of various FDA-approved medications for weight loss are presented, including placebo-controlled or, when available, head-to-head trials. Beneficial metabolic effects, including impact on liver disease, adverse effects and risks of medications are discussed, including altered gastrointestinal motility and risk for periprocedural aspiration. CONCLUSION: AOMs have established efficacy and effectiveness for weight loss even beyond 52 weeks. Further pharmacological options, such as dual and triple incretins, are probable forthcoming additions to clinical practice for combating obesity and its metabolic consequences such as metabolic dysfunction-associated steatotic liver disease.

Recent developments in diagnosing bile acid diarrhea.

INTRODUCTION: Bile acid diarrhea (BAD) commonly causes chronic diarrhea. Symptoms may be mistaken for disorders of gut brain interaction. Due to the lack of widely available diagnostic tests and poor recognition of BAD, there is a delay in diagnosis leading to increased healthcare system burden and decreased patient quality of life. AREAS COVERED: A thorough review of the literature was conducted using PubMed for articles on the biological functions of bile acids, pathophysiology and management of BAD, but focusing on diagnostic testing including 75SeHCAT retention, 7αC4, FGF-19, fecal bile acids, and single stool tests. This narrative review discusses available modalities focusing on noninvasive stool and serum testing that are more widely available and show good sensitivity and specificity for diagnosis of BAD. 75SeHCAT retention is not available in many countries. Alternative diagnostic tests include total and primary fecal bile acid (BA) excretion in 48-hour collection or a single stool sample, serum7αC4 >46 or 52.5 ng/mL, and combination of single stool and serum 7αC4 ±watery stools (Bristol Stool Form Scale 6-7). EXPERT OPINION: Given the ease of serum and single stool sample acquisition and diagnostic advances, clinical practice should embrace positive diagnosis, rather than BAS therapeutic trial. BAD needs to be considered in diverse gastrointestinal diseases.

Effects of GLP-1 and Other Gut Hormone Receptors on the Gastrointestinal Tract and Implications in Clinical Practice.

Agonists targeting the receptors of incretin hormones, glucagon-like peptide-1 and glucose-dependent insulinotropic peptide, have been well established for the treatment of type 2 diabetes mellitus. There is increasing awareness that gastroenterologists and hepatologists should be treating obesity when patients present to their clinics. In addition, gastroenterologists and hepatologists should be aware of the effects of these classes of medications prescribed by other providers. Therefore, given the widespread use of incretin agonists for obesity treatment and weight loss, it is important to recognize their effects in the gastrointestinal tract, which could constitute significant benefits in weight loss and cardiometabolic benefits, but can be associated with adverse effects that constitute a potential barrier to their use, particularly at higher doses. Multiple studies reviewed in this article document the diverse effects of these drugs on the glucagon-like peptide-1 receptors that are widely expressed in the human body, including the nervous system modulating appetite, the gastrointestinal tract modifying gastric emptying, and lipid metabolism regulation leading to reduction in fat deposition. The objective of this review is to summarize the mechanism of action of incretin receptor agonists, their effects in the gastrointestinal tract, and implications in clinical practice, particularly in the practice of gastroenterology, endoscopy, and surgery.

Optimal measurement of gastric emptying of solids in gastroparesis or functional dyspepsia: evidence to establish standard test.

OBJECTIVE: Symptoms in gastroparesis (Gp) and functional dyspepsia (FD) overlap; using egg protein substitute to measure gastric emptying of solids (GES), ~40% of patients are reclassified from Gp to FD, and vice versa. Our aim was to assess inter-individual and intra-individual coefficients of variation (COV) in GES in symptomatic patients with Gp or FD with documented slow or normal GES, respectively. DESIGN: Scintigraphic GES (T1/2 and GE% at 2 and 4 hours) using a 320 kcal real egg meal (30% fat) was tested in the following: single measurements in 20 patients with diabetes mellitus (10 each type 1 and type 2); repeat GES to estimate COVintra measured: 3 days apart in 9 Gp, 4 weeks apart in 21 Gp and 18 with FD with normal GE assigned to placebo and in 70 patients at 94.3 weeks (median) apart. RESULTS: COVinter for GE% at 4 hours and GE T1/2 were respectively 14.2% and 23.5% in FD and 27.5% and 33% in Gp; COVintra for GE% at 4 hours and GE T1/2 up to 4 weeks apart were 23.4% and 37.9% in FD and 20.1% and 33% in Gp. GE% at 2 hours showed less consistent results. However, >85% retained original diagnosis as normal or delayed. From clinical GES to baseline research for Gp group, repeat GES (after treatment) showed the COVintra for GE% at 4 hours was 37.3% at median 94.3 weeks, with 26/70 changed diagnoses. CONCLUSION: The 320 kcal (30% fat) GES scintigraphic test provides consistent diagnosis in >85% and should be the standard test for suspected gastric emptying disorders.

Left Upper-Quadrant Appendicitis in a Patient with Congenital Intestinal Malrotation and Polysplenia.

BACKGROUND Appendicitis is the most common cause of abdominal pain requiring emergent surgical intervention. Although typically presenting as right lower-quadrant pain, in rare cases it may present as left upper-quadrant pain secondary to abnormal position due to intestinal malrotation. Since atypical presentations may result in diagnostic and management delay, increasing morbidity and mortality, accurate and prompt diagnosis is important. Therefore, acute appendicitis should be considered in the differential diagnosis of left upper-quadrant abdominal pain. In this setting, medical imaging plays a key role in diagnosis. We report a case of a 13-year-old female with undiagnosed intestinal malrotation presenting with left-sided acute appendicitis. CASE REPORT A 13-year-old Hispanic female presented at the emergency room with anorexia and left upper-quadrant abdominal pain with involuntary guarding. The laboratory work-up was remarkable for elevated white blood cell count and elevated erythrocyte sedimentation rate. A nasogastric tube was placed and abdominal x-rays performed to rule-out bowel obstruction, showing distended bowel loops throughout all abdominal quadrants, with sigmoid and proximal rectal gas, raising concern for ileus rather than an obstructive pattern. Lack of symptomatic improvement prompted an IV contrast-enhanced abdominopelvic CT, revealing intestinal malrotation and with an inflamed left upper-quadrant appendix. Surgical management proceeded with a laparoscopic Ladd's procedure. CONCLUSIONS Acute appendicitis may present with atypical symptoms due to unusual appendix locations, such as in malrotation. Most cases are asymptomatic until development of acute complications, requiring imaging for diagnosis. Clinicians and radiologists should have a high index of suspicion and knowledge of its clinical presentations to achieve early diagnosis and intervention.