Context: Tirzepatide is a dual glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1 RA) approved by the US Food and Drug Administration in May 2022 for patients with type 2 diabetes mellitus (T2DM).Objective: We aimed to determine the rates of individual adverse events (AEs) related to 3 studied doses of tirzepatide.Methods: We performed a systematic review with meta-analysis including 5 databases (PubMed, Embase, CINAHL, Scopus, and Web of Science) for all clinical trials reporting AEs related to tirzepatide. The safety data from individual studies were extracted and analyzed through meta-regression to assess rates of individual AEs. Study quality assessment was performed using the National Heart, Lung, and Blood Institute Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies.Results: Ten trials (6836 participants) were included. Gastrointestinal (GI) AEs were the most commonly reported AEs and were dose dependent 39% (95% CI, 35%-43%), 46% (95% CI, 42%-49%), and 49% (95% CI, 38%-60%) for the 5, 10, and 15 mg dose, respectively. Among all GI AEs, nausea and diarrhea were most frequent at any dose of tirzepatide. Drug discontinuation due to AEs was highest with the 15 mg dose of tirzepatide (10%). Incidence of mild hypoglycemia (blood glucose < 70 mg/dL) was highest with tirzepatide 10 mg dose 22.6% (9.2%-39.8%). Rates of fatal AEs, severe hypoglycemia, acute pancreatitis, cholelithiasis, and cholecystitis were extremely low (≤ 1%) across all doses of tirzepatide.Conclusion: Tirzepatide is associated with a dose-dependent increase in incidence of GI AEs and AEs leading to drug discontinuation. Severe hypoglycemia, fatal AEs, acute pancreatitis, cholelithiasis, and cholecystitis are rare with this medication.

Culturally-appropriate family models of diabetes self-management education and support (DSMES) using community health workers (CHWs) have been shown to help address barriers to improving type 2 diabetes mellitus (T2DM) self-management for racial/ethnic minority communities; however, there is limited DSMES research among Marshallese and other Pacific Islanders. Using a community-based participatory research approach, we engaged community stakeholders to co-design a study to implement a culturally adapted family model DSMES (F-DSMES) intervention in faith-based organizations (FBOs) (i.e., churches). Using a cluster-randomized controlled trial design, we will assess the effectiveness of the F-DSMES intervention for Marshallese patients with T2DM in Arkansas and Oklahoma. Twenty-four FBOs (with 12 primary participants per FBO) will be randomized to one of two study arms: the intervention arm or the wait-list control arm. Primary participants must have at least one family member willing to attend education sessions and data collection events. The F-DSMES intervention consists of ten h of diabetes education delivered by CHWs over eight to ten weeks. Data will be collected from the intervention arm at pre-intervention (baseline), immediate post-intervention (12 weeks), and three months post-intervention. The wait-list control arm will complete a second pre-intervention data collection before receiving the intervention. The primary study outcome will be glycemic control, as measured by HbA1c. Secondary measures include glucose, weight, body mass index, blood pressure, diabetes self-management behaviors, and diabetes management self-efficacy. The knowledge gained from this research will inform future DSMES and other health promotion interventions conducted with Marshallese and other Pacific Islander communities.

Adrenal mixed corticomedullary tumors (MCMTs) are composed of an admixture of cortical and medullary cells. Owing to the presence of two distinct components of different embryonic lineage, these tumors are extremely rare. Less than 30 tumors of this type have been reported to date. MCMTs have varied presentation including hypertension, Cushing syndrome or even as adrenal incidentalomas. Also noted is a slightly higher female preponderance. We report a case of a 26-year-old female who was evaluated for uncontrolled hypertension. A renal ultrasound followed by MRI abdomen revealed a 9.3 × 8.1 × 7.0 cm partially cystic, partially solid enhancing mass in the region of/replacing the left adrenal gland. Hormonal work-up was significant for elevated catecholamines concerning pheochromocytoma. She underwent laparoscopic left adrenalectomy, with adequate pre-operative adrenergic blockade. Histology and immunochemical testing were consistent with a mixed corticomedullary tumor. She was monitored annually for recurrence of the tumor. We also performed a comprehensive review of literature of the cases published so far to the best of our knowledge.

The Republic of the Marshall Islands (RMI) has a high rate of type 2 diabetes mellitus (T2DM). To address the high rate of T2DM, we tested a culturally adapted family model of diabetes self-management education and support (F-DSMES). We report the results of the 12-month post-intervention data collection and describe the lessons learned from the delivery of the F-DSMES intervention. Recruitment took place in four churches in Majuro and included 10 h of content delivered over 8-10 weeks. Forty-one participants with T2DM were included. The primary study outcome was glycemic control measured by a change in HbA1c. We also conducted participant interviews to document the participant-reported barriers encountered during the F-DSMES intervention. Participants did not show improvements in their biometric markers; however, participants did show improvement on multiple measures of diabetes knowledge and family support. We identified five areas to improve future interventions: 1) issues with recruitment, retention, and attendance; 2) needing help accessing information and additional healthcare provider counseling; 3) struggles with adhering to diet recommendations; 4) difficulty getting exercise, and 5) improving lessons within the intervention. Although the biomarker data did not show improvement, valuable information was gained to improve the development of larger-scale trials. The results provide evidence of the need for these trials and the desire of participants to continue pursuing this effort. Others doing similar work in other low-to-middle income countries will need to take into consideration the potential barriers and facilitators within participants' social and physical environments.

Pancreatic neuroendocrine tumors secreting gastrin and adrenocorticotropic hormone (ACTH) are rare. The presentation of the cases can be varied, making the diagnosis challenging and often delayed. Here, we present a patient who presented with severe hypokalemia and was found to have ectopic Cushing’s syndrome. An abdominal CT scan showed a pancreatic lesion with metastatic liver disease. A biopsy of the liver lesion confirmed a metastatic neuroendocrine tumor. The final diagnosis was ectopic ACTH-producing metastatic gastrinoma. Twenty-four-hour urinary cortisol was significantly elevated at 9,790 mcg/24 hours. The excess hormonal secretion was successfully treated with ketoconazole and somatostatin analogs. She was further started on chemotherapy with capecitabine plus temozolomide, which has become the preferred chemotherapy treatment after the results of the recently completed trial. She also received Y90 therapy for metastatic liver disease. The prognosis of metastatic pancreatic neuroendocrine tumors is poor. Multidisciplinary combined therapies can help control disease and improve prognosis. We present an 18-month-long patient follow-up and a literature review of ectopic ACTH-producing metastatic gastrinomas.